Gastrointestinal disorders such as peptic ulcers, gastroesophageal reflux and heartburns arising out of excessive secretion of acidic gastric fluids are amongst the widely encountered diseases in modern age. These diseases, if not controlled, have a tendency to aggravate and ultimately result in gastric cancer. The initial treatment for this indication involved use of histamine-H2-receptor antagonists such as cimetidine as acid secretion inhibitors, which was later followed by introduction of the proton-pump inhibitors (PPIs), collectively known as the prazoles.
The vast majority of the proton-pump inhibitors belonging to prazole group of compounds are benzimidazole derivatives comprising of two heterocyclic moieties, imidazole and pyridine which are linked through a methylene sulfinyl [—CH2S(O)—] group. The mode of action involves inhibition of gastric acid secretion in the lumen of the stomach by blockage of (H+/K+)ATPase enzyme of the parietal cell, which is responsible for gastric acid production and is located in the secretory membranes of the parietal cells. Incidentally, the prazole group of compounds are by themselves, not active inhibitors of this enzyme but are transformed within the acid compartments of the parietal cells into the active inhibitors.
Portugaliae Electrochimica Acta (2008), 433-448 discloses that in case of omeprazole, the inactive drug is converted to its active form by a probable mechanism which involves protonation and removal of a water molecule to form a sulfenamide intermediate of formula (P1). This intermediate reversibly reacts with the sulfenic acid from which it has been generated and leads to the molecule (P2), which possesses a disulfide linkage between the benzimidazo pyridine fragments. (Scheme-1)

The intermediate (P1), as discussed in Acta Chemica Scandinavica (1989), 43, 536-548, also undergoes aryl oxygen cleavage on treatment with hydrochloric acid to provide a pyridone derivative (P3) (Scheme-2).

The pyridone derivative (P3) gets further converted to compound (P4), similar to the disulfide compound (P2). Herein, it is pertinent to note that the pyridone derivative (P3) is known to be an unstable intermediate in the reactions of prazoles occurring in the acidic environment and readily converts to the disulfoxide derivative (P4).

It has also been reported that sulfenamides characterized by structures similar to compound (P1) are difficult to isolate and are usually isolated as acid addition salts.
U.S. Pat. No. 4,636,499 discloses methods for the preparation of the sulfenamides which can be employed for providing gastrointestinal cytoprotective effects during the treatment of gastrointestinal inflammatory diseases in mammals. The process comprises treatment of the respective prazole having a sulfoxide functional group with prohibitively expensive acids like HPF6, HBF4 or HAuCl4. Hence, the resulting sulfenamide is in the form of an acid addition salt with the said acids, which unfortunately cannot be administered as such and needs to be converted to its free base followed by optional treatment with pharmaceutically acceptable acids.
U.S. Pat. No. 4,769,456, U.S. Pat. No. 5,162,317 also discloses methods for preparing sulphenamides, which apparently due to difficulty in isolation of the product are isolated as their salts with costly acids like fluoroboric acid, tetrafluoroboric acid or hexafluorophosphoric acid and not suitable for therapeutic use.
The present inventors, while carrying out research for identifying compounds that are themselves active inhibitors of gastric acid secretion in the stomach, through serendipity were successful in isolating compounds of formula (I) in a stable form. These compounds were found to exhibit instant therapeutic action against gastrointestinal disorders, without being converted further into any other active form.

wherein, R1, R2 and R3 are independently alkyl, alkoxy, halogen, halogenated alkoxy, halogenated alkyl, hydrogen and could be the same or different and X is CH or N,
R1 is methyl, methoxy, fluorine, trifluoromethyl, difluoromethoxy and hydrogen,
R2 is methyl, methoxy and hydrogen,
R3 is methyl and hydrogen.
After an extensive study of the literature reports relating to the active compounds for gastrointestinal secretion inhibitory activity of prazoles, it was found that compounds of the invention having formula (I) were novel. Earlier, it was not possible to synthesize or isolate these compounds due to their unstable nature. Further, it was also found that the invented compounds having the pyridone moiety and the disulfide linkage were different from similar disulfide compounds (compound P2) disclosed in International Journal of Pharmaceutics (2006), 323, p.110-116.
Another noteworthy finding about compounds of formula (I) was that they were found to be at least six times more potent than the prazole compounds, This would significantly lower the dosage of the active ingredient and also minimize any untoward side effects that are associated with higher dosage as compared to prior art compounds having similar therapeutic action.
The compounds of the embodied invention were prepared and isolated as stable, crystalline or amorphous solids, depending upon the structure of the compound and the method employed for their isolation.